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Cardiovasc. Res., 1969, 3, 476-485.

Cardiovascular and Respiratory Changes During Sleep

in Normal and Hypertensive Subjects
and P. SLE[GHT
From the Cardiac and Regius Professor of Medicine’s Departments, Radcliffe Infirmary, Oxford

AUTHORS’ SYNOPSIS.Thefall of bloodpressure accompanying sleep in man is largely due to a dimin-

ished peripheral resistance. Subjects with normal and raised arterial pressure show qualitatively and
quantitatively similar haemodynamic changes during sleep, except that the baroreflex sensitivity in
hypertensives is decreased, both awake and asleep.

Sleep, once described as “the diastole of the system shows a redistribution of activity in sleep,
cerebral beat” (Duckworth, 1881) is now generally the general trend being towards an enhancement of
thought to be an active process, with distinct parasympathetic over sympathetic activity, with
brain-stem mechanisms necessary to produce the miosis and bradycardia. Both blood pressure
two types of sleep-orthodox or slow wave sleep, and heart rate fall, and it has been recently shown
and paradoxical or rapid eye movement (REM) by Smyth, Sleight, and Pickering (1969) that in
sleep (Jouvet, 1967). The autonomic nervous man the heart rate-blood pressure reflex is actively
maintained during these changes. The present
Accepted March 4, 1969. study, from the same laboratory, was of a further
* Present address: University of Oregon Medical School, series of subjects and, in addition, cardiac output
Portland, Oregon, U.S.A. and blood gas changes were measured, and normal
t M.R.C. Fellow. Reprint requests to T.G.P., Cardiac
Department, Radcliffe Infirmary, Oxford. subjects compared with hypertensives.

Table 1. Subjects Investigated, Arranged According to their Mean Arterial Preswres Awake*

Subject Age Sex MAP awake Diagnosis

no. (mm Hg)
1 36 M
2 46 M
3 24 M
4 23 F
5 39 M 89
6 24 M 90
7 45 F 92 Normal-referred for ? hypertension
8 48 M 93 Normal-referred for ? hypertension
9 58 M 104 Essential hypertension
10 55 F 111 +
Hypertension renal disease
11 35 M 112 Essential hypertension
12 50 M 1I4 +
Essential hypertension bronchiectasis
13 41 M 116 Essential hypertension
I4 55 F 118 +
Hypertension renal disease
15 50 M 120 Essential hypertension
16 44 M 131 Essential hypertension
17 52 F 136 Essential hypertension
18 29 F 137 Essential hypertension
19 55 M 130 Postural hypotension + chronic

* The dividing line between normals and hypertensives was arbitrarily taken as 100 mm Hg.
Cardiovascular Changes During Sleep 477
Methods frequency response characteristics of the recording
system were determined by applying a square wave
Nineteen subjects were investigated; their ages
pressure pulse at the cannula tip: the time constant was
ranged from 24 to 58 yr. Some were volunteers with
25 msec and the resonant frequency 11 c/s. Respiration
normal blood pressure, whereas others had been re-
ferred for further investigation of hypertension. As was recorded by a pneumograph round the chest con-
nected to another strain gauge, and the electrocardio-
shown in Table 1, they were separated into two groups,
gram (ECG) from two precordial electrodes. The
eight having mean arterial pressures (MAP) of less than
EEG was taken from five pairs of bipolar electrodes on
100 mm Hg-the normal group-and 10 with MAP of
more than 100 mm Hg-the hypertensive group. One the right hemicranium; eye movements and submental
electromyogram (EMG) were recorded as described
subject (No. 19) had severe chronic bronchitis and
previously (Smyth et al., 1969). The different stages of
postural hypotension, and was not included in either
sleep and wakefulness were defined according to the
group. The average age for the normal group was 35, criteria of Gastaut and Broughton (1965). Typical
S.D. 10.6 yr, and for the hypertensives 47, S.D. f 8.9.
records showing the 10 channels used are shown in
All the subjects slept for three consecutive nights in Fig. 1.
the laboratory. On the first night systemic arterial
pressure was recorded every 5 min by an automatically
Baroreflex Sensitivity
inflated sphygmomanometer cuff, as described by
Richardson, Honour, Fenton, Stott, and Pickering Rapid intravenous injections of angiotensin (0.25-
(1964); on the second night continuous electroence- 1.0 pg) or phenylephrine (25-100 pg), flushed in with
phalogram (EEG) recording was added. During the 10 ml. saline, were used to produce brief rises of arterial
third night continuous recordings of brachial intra- pressure of up to 30 mm Hg, with consequent reflex
arterial pressure were obtained through a fine (1 mm bradycardia. After such an injection, each peak of
internal diameter) polyethylene cannula 15 in. long systolic pressure is correlated with the duration of the
connected to a Consolidated Electrodynamics strain pulse interval following the next beat; a linear plot is
gauge by a 4 ft. polyethylene tube. Arterial blood obtained with a correlation coefficient of the order of
could be withdrawn through this without disturbing 0.7-0.9. The slope of the line so obtained is an index of
the patient. A second cannula 9 in. long was inserted baroreflex sensitivity, and is expressed in msec/mm Hg
into an antecubital vein for intravenous injections. The ---that is, the absolute increase in pulse interval produced

Respiration --.-.----

Fig. 1. EEG changes during sleep and wakefulness. From above downwards: top five tracings EEG
(International 10-20 notation), EMG, eye movements, ECG, respiration, and brachial intra-arterial pres-
sure. Subject awake, BP= 170/90, in Stage 111 sleep, BP= 150/70, and in R E M sleep, BP= 155/75.
478 Bristow, Honour, Pickering, and Sleight
by a 1 mm rise in systolic BP. This method has been hypotension. The waking pressure was taken as
fully described by Smyth et a / . (1969). The lines ob- the average of 5 min readings whenever the subject
tained by either angiotensin or phenylephrine were was awake-before sleep, during wakeful periods
consistently repeatable (Bristow, Pickering, and Sleight, in the middle of the night, a n d after sleep, t o mini-
1969), and the results with phenylephrine were not mize changes due t o circadian rhythms. Readings
significantly different from those with angiotensin,
except that the occasional tachycardia at the end of the less than 5 min after a phenylephrine injection were
pressure rise seen with angiotensin was not found with excluded. The degree of fall of pressure was
phenylephrine. The responses to the two drugs have roughly proportional t o the waking pressure, the
been considered to be identical. The earlier subjects fall of MAP being 9.7, S.D.+8.3% (8.3 mrn Hg)
were tested with both, but later phenylephrine alone for the normals, and 11.7, S.D.k5.2% (13.4
was used. These injections were done throughout the m m Hg) for the hypertensives. Systolic pressure
night, without the subjects’ awareness of when they were fell more than diastolic, so that the pulse pressure
being performed. Most subjects had about 15 injec- was 6.0, S.D.k 3.2 m m H g less during sleep in the
tions in all. Control injections of saline had no effect normals, and 9.6, S.D. & 6.6 m m H g in the hyper-
on heart rate or blood pressure.
tensives. The lowest pressures were generally seen
Cardiac Output either in stage I V or R E M sleep. Results for the
two phases of sleep were analysed separately.
The Stewart-Hamilton dye dilution method was used,
with injections of 5 mg of indocyanine green flushed into Heart rate fell during sleep in all but four sub-
the venous cannula by 10 ml. saline. Blood was with- jects (subject 19 again showing n o change) a n d
drawn from the arterial cannula through a cuvette there was n o significant difference between the two
densitometer (Cambridge Instrument Co.) by a with- groups, the changes being 6,4, S.D. k 6.4%, or
drawal pump at 23 ml./min, and the resulting curve
recorded on film. All determinations were done in
5.0 beats/min for the normals, and 7.0, S.D. 5.1%, +
or 4.7 beats/min for the hypertensives. Waking
duplicate; MAP (by electrical damping of the arterial heart rates were slightly higher in the hypertensive
record) and heart rate were measured at the same time.
Most subjects had three such pairs of injections during group, but there was n o correlation between the
the course of the night. waking heart rate and the degree of bradycardia
with sleep; nor was there a coiisistent relationship
Blood Gases between the degree of fall OF pressure and the
Heparinized syringes were used to take 7 ml. samples degree of bradycardia for each subject, apart from
of arterial blood which were analysed immediately on a the fact that both tended to fall, as shown in Fig. 2.
Radiometer apparatus for pCO,., pOz, and pH. The All subjects were in sinus rhythm, although one
calibration was checked with standard gases and buffer (No. 15) had frequent premature atrial contractions
for each measurement. Each subject had at least four
such determinations during the night.
The third night of the study provided all the results
reported here. The subjects arrived at the laboratory
at 9.30 p.m., and recordings were started about 1) hr
later. Waking recordings were taken with the subject
lying quietly in bed, at least 30 min after the insertion
of the arterial and venous lines. Cardiac outputs were
recorded before the injections of phenylephrine or
angiotensin, as the latter might produce transient
changes in output. The samples for blood gases were
taken last of all, just before turning out the lights at
about 11.30 p.m. These procedures were repeated
throughout the night. The subjects were awakened
at about 4-5 a.m. and waking records were taken for a
further 30 min. None of the subjects was sedated, and
none was receiving hypotensive therapy at the time of

Blood Pressure and Heart Rate Fig. 2. Changes in heart rate plotted against changes in
Values for each were taken every 5 min. There mean arterial pressure occurring with sleep. Each point
was a fall of blood pressure with sleep (systolic, represents one subject. Although both fall in most subjects,
there is not a consistent relation between the two for any one
diastolic, and mean pressures) in all but two sub- subject. 0 =normal. 0 =hypertensive. W = postural
jects, one of whom was subject 19 with postural hypotension.
Cardiovascular Changes During Sleep 479
Pulse 1 nterval Subject No. 18
1200 m sec





700 '





190 200
1 1

S y s t o l i c P r e s s u r e m m Hg
Fig. 3. Baroreflex changes with sleep in one subject. Each line represents one injection of phenylephrine.
A=average systolic pressure awake, both before and after sleep. S=average systolic pressure during
slow wave sleep.

which persisted throughout wakefulness and sleep, the left-that is, resetting the reflex-or by a com-
and made calculations of the reflex sensitivity im- bination of the two. This is shown diagram-
possible. matically in Fig. 4, where it is assumed that the
linear relationship which we have observed during
Baroflex Sensitivity a transient pressure change represents a portion of
Comparisons between waking and sleeping re- a sigmoid curve, as originally described for the
flex sensitivity were made in 15 subjects. Hyper- carotid sinus response by Koch (1 93 I).
tension is characterized by a reduced baroreflex The subject whose reflex changes are demon-
sensitivity when tested by this method (Bristow,
strated in Fig. 3 showed both phenomena. Her
Honour, Pickering, Sleight, and Smyth, 1969); the
reflex sensitivity increased from 4.1 mseclmm Hg
normal group had a mean waking sensitivity of
to 8.0 (P<O.OOl), and the lines obtained during
14.8, S.D.f9.2 mseclmm Hg, and the hyperten-
sleep are clearly separated from those of wakeful-
sives 3.0, S.D. kO.9 msec/mm Hg. Subject 19 ness, indicating that resetting has occurred. To
with postural hypotension had the lowest sensitivity
obtain a quantitative index of resetting we have used
of all--0.3 msec/mm Hg.
the vertical distance between the lines at an arbi-
The changes occurring in sleep in one subject (No. trary reference pressure, which is the averaged wak-
18) are shown in Fig. 3, each line representing the ing systolic pressure A, and the measurement is
response to one injection of phenylephrine. The expressed in milliseconds (Fig. 5 ) . This index,
averaged heart rate-systolic pressure relationships however, will be influenced both by changes of
for the whole night separated for wakefulness (A) slope of the lines and by shift of position. We have
and sleep (S) are superimposed, and it can be separated these by drawing a line from the origin
seen that, although the baroreflex mechanism is of the averaged line for sleep parallel to the line
still active during sleep, an alteration of the reflex for wakefulness. This line represents the change
must have occurred to allow the different heart due to resetting alone, and its shift from the waking
rate-systolic pressure relationships which were line is given by R. The effect of altered sensitivity
observed during wakefulness and sleep. is given by S. Positive resetting is taken as a shift
This alteration could be brought about either by of the lines towards an increase in pulse interval
changing the slope of the lines-that is, altering the (and an increased reflex activity), and negative
sensitivity of the reflex-or by shifting the lines to resetting as the reverse.
480 Bristow, Honour, Pickering, and Sleight

Systolic Pressure
Fig. 4. Theoretical baroreflex changes with sleep. Heavy lines indicate observed phenylephrine induced
changes. These have been superimposed on theoretical S-shaped curves describing the bchaviour of the
reflex arc over a wide range of pressure. Resetting has occurred when the control pressure-pulse interval
relationship is altered, change in reflex sensitivity occurs with change of slope. A =awake. S=sleep.
0 =average control systolic pressure before injection.

Table 2 shows the changes occurring with sleep in difference may lie in the lesser number of in-jections
each of the 15 subjects tested, separated into changes carried out in REM sleep during the present study
due to altered reflex sensitivity and those due to (the results shown in Table 2 are only for slow wave
resetting. Comparing these results with those sleep). In all five of the subjects of this series
reported earlier (Smyth et al., 1969), we now find tested in REM sleep (four normals and one hyper-
only one-third of subjects increasing the slope of tensive) there was an increase in reflex sensitivity
their lines during sleep, compared with nine out of when compared with waking slopes. In the earlier
10 in the earlier series. Indeed, in the present study, injections during REM sleep were obtained in
series a significant fall of reflex sensitivity was as seven of the 10 subjects, and in six of the seven these
common as an increase. One explanation of this injections provided the highest slopes of the night.

Table 2. Buroreflex Changes with Sleep, Analysed According to Changes in Sensiticity and Resetting
Average slopes (msec/mm Hg) Pulse interval (msec) at rel'erence pressure
(average waking systolic pressure)
Subject Awake Injects., Asleep Injects., Differ- P Awake Asleep Differ- P Change due to
no. no. no. ence ence - altered
I sensitivity
1 12.3 8 16.9 4 + 4.6 NS 940 1300 +360 <O.OOI + 260 + 100
2 8.5 5 10.1 4 + 1.6
- 8.2
< 0.02
< 0.001
++ 250
60 + 40
- 50
3 22.4 8 14.2 5
4 29.3 10 26.3 3 - 3.0 < 0.05 910 1380 +370 <0.001 + 540 - 70
5 10.4 10 8.2 5 - 2.2 < 0.01 980 970 - 10 <0.05 0 - 10
6 23.5 6 13,6 4 - 9.9 < 0.002 1070 1440 +370 <O.OOI + 630 - 260
7 3.6 10 2.7 7 - 0.9 < 0.001 790 950 +I60 <O.OOI + 180 - 20
8 4.4 9 5.9 11 + 1.5 < 0.001 970 1040 + 70 <0.001 + 30 + 40
9 1.8 7 I .8 4 0.0 NS 810 900 + 90 <0.001 + 90 0
10 2.4 6 0.4 4 - 2.0 NS 810 830 + 20 <0.002 + 20 0
11 3.3 5 5.2 7 + 1.9 < 0.002 800 960 + 160<0.002 + 120 +- 40
13 3.9 10 2.6 2 - 1.3 NS 680 800 +120 NS + 85 25
16 2.7 6 3.8 6 + 1.1 NS 1120 1280 +160 <0.001 ++ 100
70 ++ 180
18 4. I 3 8.0 6 + 3.9 <0.001 820 1100 +280 <0,001
19 0.3 3 0.0 3 -0.3 NS 1 910 880 - 30 NS - 30 0
Cardiovascular Changes During Sleep 481
The resetting of the reflex mechanism is much +
normals, a n d 80, S.D. k 34 msec for the hyper-
more constant. In 12 of the 15 subjects it occurred tensives. This difference is due to the steeper
in the direction of lowered heart rate and blood slopes of the normal subjects, as shown in Fig. 5 ,
pressure (positive resetting); in another subject which compares the changes shown i:i two subjects,
(No. 13) resetting was insignificant; in subject No. one normal and one hypertensive, who showed
19, who had the smallest change in heart rate and similar changes in blood pressure and heart rate.
blood pressure, together with the lowest reflex Resetting of the lines during R E M sleep was less
sensitivity, it did not occur, and in one other subject marked than changes in sensitivity; in three sub-
(No. 6) it went the other way. The blood pressure jects the lines were reset more during R E M sleep
of this subject did drop with sleep (7 m m fall of than slow wave sleep and in two subjects less.
MAP), but his heart rate was unchanged.
The resetting that accompanied sleep was usually Cardiac Output
only partially reversed o n waking, so that the lines
Measurements were carried out in 17 subjects
obtained after sleep were intermediate in position
(seven normals, nine hypertensives, and subject
between sleep and pre-sleep wakefulness. This was
No. 19), with a total of 5 5 pairs of observations.
seen in all 11 subjects for which such data were
For each pair the mean difference between the two
available, and was reflected by the generally lower
determinations was f 6.4%, S.D. f4.5%. Two of
blood pressure during the 30 min after sleep than
these subjects did not sleep and in both of these the
in the 30 min preceding it. This may well be due
outputs measured early and late in the night, about
to the early hour (4-5 a.m.) at which such post-
4 hr apart, were within 5% of each other.
sleep testing was done, as other workers have found
that pre- and post-sleep levels are the same (Khatri There was no significant difference between the
a n d Freis, 1967a), a n d there is a circadian rhythm waking outputs of the two groups, the average for
of blood pressure in addition to the effect of sleep the normals being 5.1 5 , S.D. f.1.48 I./min, and for
(Richardson et a/., 1964). the hypertensives 5.28 S.D. f 1.73 I./min.
The degree of resetting in the two groups of During sleep the normals showed no consistent
patients was significantly different ( P c O a ) , the change in cardiac output (sleep values compared
averages being +244, S . D . k 2 2 3 msec for the with average pre- and post-sleep waking values);

Pulse Interval /’ Subject No. 1


Subject No. 12

- /
J - k-.... AWAKE

800 - %
1 I I I I I I I I I J
80 100 120 140 160 180
Systolic Pressure mm Hg
Fig. 5. Waking and sleeping slopes in a normal (No. I ) and a hypertensive (No. 12) subject. Lines
represent averaged values of individual injections. The shifts of the lines have been divided into the contri-
bution due to resetting (R) and due to change in sensitivity (S). These values are taken arbitrarily at
the waking systolic pressure.
482 Bristow, Honour, Pickering, and Sleight
there was a variable fall of 6.2% S.D. k 13.6% in the subjects, one of whom had bronchiectasis, and the
hypertensives, but this change was not statistically other of whom showed an unexpectedly low PaOz.
significant. The values obtained before sleep were Changes observed in sleep were consistent in all
generally slightly higher than those after sleep. subjects.
Satisfactory measurements in REM sleep were The PaCOz rose by 4.0 S.1). k 1.8 mm Hg, the
obtained in only two subjects (both with normal PaOz fell by 5.4 S.D.kS.1 mm Hg, and the pH
pressures) and in both of these the levels were fell by 0.014 S.D. & 0.012. There was no obvious
higher than the mean values for waking or slow correlation with the depth of sleep, or the time of
wave sleep. night, except that the pH tended to be lower in the
Total peripheral resistance (TPR), calculated latter part of the night. The subject who showed
from cardiac output and MAP at the time of the largest fall of PaOz ( I 3 mrn Hg), although not
measuring the output, fell significantly (P< 0.02) the largest rise of PaCO2, was the only one who
in all but one subject (No. 9). There was a tend- snored persistently throughout the night. These
ency for larger falls of TPR to occur in subjects changes in blood gases were associated with brady-
with higher mean waking pressures. This, how- cardia and hypotension during sleep.
ever, was not statistically significant because of the REM sleep measurements were obtained in four
one subject whose TPR increased markedly during subjects: the PaOz and PaCOZ were no different
sleep. If his results are omitted (and this output from the values seen during slow wave sleep, but
was a single measurement, not a pair) the relation- in three of the four the pH was lower during REM
ship does become significant (r = 053, P = 0.05), sleep than at any other time.
as shown in Fig. 6. On waking, the blood gases returned to approach
Both groups of subjects showed bradycardia the pre-sleep levels, and, although the pH and pCOz
during sleep, and if the heart rates at the time of changes were not always fully reversed, the differ-
measuring cardiac outputs are taken, the calculated ences between pre- and post-sleep levels were in-
stroke volumes show an insignificant (0.05 < significant.
P<O.l) increase of 11.2 ml. for the normals, with
no change for the hypertensives.
Blood Gases The most constant haemodynamic changes with
Forty-four observations were made in 10 sub- sleep which we have observed were the fall of blood
jects. Waking values were normal in all but two pressure and of TPR, both of which occurred in all
but one subject (No. 19 for blood pressure, No. 9
for TPR). In all subjects except No. 19 sleep was
Fall of 1 P R with Sleep accompanied by a fall of MAP of about lo%,
Arbitrary units
and a fall of heart rate of 72;. Of the 10 hyper-
tensive subjects, seven still had a MAP of more
than 100 mm Hg during sleep, only two falling
below this level (the remaining subject did not sleep).
These pressure changes are similar to those re-
ported previously for normal subjects (Snyder,
Hobson, Morrison, and Goldfrank, 1964; Khatri
and Freis, 1967a) and hypertensives (Richardson
2.23 et al., 1964). Shaw, Knapp. and Davies (1963)
found that patients in the malignant phase of
hypertension showed very little change; all our
hypertensives were in the benign phase.
Such a fall of arterial pressure could either be
due to a fall of cardiac output, or to a fall of TPR,
or to a combination of both. Our results indicate
that the lower pressure during sleep is primarily
due to a fall of TPR, with an insignificant fall of
cardiac output occurring in hypertensives. The
70 80 90 1W 110 120 130 140 150 only other measurements of cardiac output in man
M A P Awake mm HS during sleep are those of Khatri and Freis (1967a,
Fig. 6. Fall of TPR with sleep plotted against waking MAP. b), who reported a drop of 10% in normal subjects.
Cardiovascular Changes During Sleep 483
They concluded that the fall of blood pressure was animals were hypertensive when awake; the same
due to the fall of cardiac output, as the calculated workers have subsequently shown that it is the
TPR remained unchanged. In hypertensives, chemoreceptors rather than the baroreceptors which
however, they did find a fall of TPR. The reasons normally prevent such changes (Guazzi, Baccelli,
for these differences are not clear, although their and Zanchetti, 1968). The subject in our series
subjects were all young healthy volunteers whose who most closely resembled the sino-aortic de-
output averaged 7.64 I./min, whereas ours was a afferented cats was the bronchitic with severe
much more varied sample with an average output postural hypotension (No. 19). In fact his blood
of 5.19 l./min, so on these grounds alone we might pressure and heart rate showed almost negligible
be less likely to detect a significant change. change with sleep (see Fig. 2), and his lesion is more
Animal experiments on this problem have been likely to be on the efferent side of the reflex arc.
mainly concerned with the blood pressure fall The contribution which the baroreceptors make
during REM sleep in the cat; and the cat differs to the regulation of cardiac output and TPR is a
from man in that the pressure falls to persistently controversial one, in animals no less than in man.
lower levels during REM sleep than at other times. The evidence suggests that baroreceptor stimula-
However, Zanchetti's group (Kumazawa, Baccelli, tion in man does lower cardiac output, and also
Guazzi, Mancia, and Zanchetti, 1967; Guazzi, decreases TPR (Carlsten, Folkow, Grimby, Ham-
Mancia, Kumazawa, Baccelli, and Zanchetti, 1968) berger, and Thulesius, 1958; Bevegird and Shep-
have found that the fall in blood pressure is largely herd, 1966).
due to a fall of TPR, since denervating the heart
in sino-aortic deafferented cats made no difference Arterial C 0 2 tension might also affect TPR, for
to the change in blood pressure with sleep, and hypercapnia induced during wakefulness is associ-
vagotomy (both surgical and pharmacological) ated withvasodilatation; however, the other changes
prevented the bradycardia but not the hypotension. seen during hypercapnia-hypertension, tachy-
They concluded that . sleep hypotension is
' I . . cardia, and increased cardiac output-do not re-
fundamentally dependent on peripheral vascular semble the changes seen in sleep. The effects of
phenomena." hypercapnia on the resetting of the baroreflex in
awake man have recently been studied (Bristow,
The role of the baroreceptors in human sleep has Brown, Cunningham, Goode, Howson, and Sleight,
been discussed previously (Smyth et a/., 1969), al- 1968) and are of particular interest as the resetting
though in this series we have found changes due occurred in the opposite direction to that seen in
to resetting more important than changes of reflex sleep (Fig. 7). Similar changes in blood gases
sensitivity. Resetting of the baroreceptors is a have been reported by Birchfield, Sieker, and Hey-
well-known concomitant of renal hypertension in
man (1958), although their pCOz levels were rather
animals (McCubbin, Green, and Page, 1956) higher than ours, both awake and asleep. Robin,
and in man (Bristow, Honour, Pickering, Sleight, Whaley, Crump, and Travis (1958) showed that the
and Smith, 1969), but in these cases it is thought to
C 0 2 response curve is flattened, which they attri-
occur at the receptor end of the reflex arc, whereas buted to a reduced sensitivity of the respiratory
the reversible resetting and altered sensitivity seen centre during sleep. However, Fuleihan, Nakada,
in sleep are presumably centrally mediated.
Suero, Merrifield, Dutton, Permutt, and Riley
Sino-aortic deafferentation in cats permits (1 963) using barbiturate-induced sleep, found no
catastrophic falls in blood pressure during sleep difference in the transient responses to COz
(Guazzi and Zanchetti, 1965), even though these breathing between sleep and wakefulness, although

Variable Normals Hypertensives

(n= 8) (n = 10)
_ _ ~ -
MAP -9.7% (S.D. 8.3%) - 11'7% (S.D. 5.2%)
Heart rate -6.4% (S.D. 6.4%) -7.0% (S.D. 5.1%)
Cardiac output No change Inconstant fall
TPR - 16.7% (S.D. 7.1%) - 16.7% (S.D. 9.3%)
Stroke vol. Inconstant rise N o change
a. sensitivity Variable change Variable change
h. resetting +244 msec (S.D. 233 msec) +80 msec (S.D. 34 msec)
484 Bristow, Honour, Pickering, and Sleight
Subject No. 2 Subject R.B.
Pulse Interval m sec. WAKEFULNESS
160 160
56.4 mmHg

140 140



80 80

1 I I 1 I I I I

Fig. 7. Effect of hypercapnia on baroreflex awake and asleep. The interrupted lines represent the resting
state, the solid lines hypercapnia. The resetting which occurs with sleep (left panel) is in the opposite
direction to that occurring when pC0, is raised without sleep (right panel).

the curves of pCOz versus ventilation rate were subjects with normal and raised arterial pressure,
shifted in the direction of a higher pCOz and lower both awake and asleep. The blood pressure falls
ventilation during sleep. These experiments are during sleep, and the absolute fall is greater in
similar in nature to our induced blood pressure hypertensives, although the percentage changes are
transients and, like them, might be interpreted on similar (10%) in both groups.
the basis of a resetting of respiratory control during Baroreflex sensitivity changes variably with sleep,
sleep. although in all five subjects so tested the sensitivity
The haemodynamic differences between the two was greater during REM sleep. Resetting of the
groups of subjects, summarized in Table 3, are reflex, with a lower heart rate for a given systolic
quantitative rather than qualitative, the slightly pressure, was seen in 12 out of 15 subjects; these
greater falls of arterial pressure in the hypertensives changes were reversed on awakening. One subject
being merely a reflection of their higher waking with autonomic denervation showed no resetting
levels, the percentage changes being very similar. and no changes in heart rate or blood pressure with
In the same way the greater baroreflex changes in sleep.
the normal subjects are paralleled by their higher There was no consistent change in cardiac output
waking sensitivities. Thus the patient with hyper- in sleep for either group although peripheral
tension differs little from others in his circulatory resistance fell significantly. PaCOz increased by
adjustments to sleep, except that he is still hyper- 4 mm Hg during sleep and PaO, decreased by
tensive, and his baroreflex sensitivity usually re- 5.4 mm Hg.
mains reduced. There does not appear to be any qualitative
difference between subjects with normal and high
Summary blood pressures in their haemodynamic adjustments
Intra-arterial blood pressure, cardiac output, during sleep except that the latter have an almost
arterial blood-gases and baroreflex changes (blood five-fold reduction in baroreflex sensitivity both
pressure-heart rate reflex) have been studied in 19 awake and asleep.
Cardiovascular Changes During Sleep 485
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